When I was asked to speak about future
national research policies, my first thought was, "That's
easy. Given the current state of knowledge, I will say there has
been no coherent policy and then I will propose one." Then,
I reconsidered my thought. Let me tell you why.

Women account for about 11.9% of participants
ever to have been in government-sponsored AIDS Clinical Trials
Groups (ACTG) research testing the outcomes of anti-HIV treatments
or treatments for opportunistic infections. With the exception
of one study, even when there have been enough women in research,
comparison of outcomes for men and women have not been done. Most
studies don't have enough women to do comparisons. In drug company
research the percent is lower. And, while there have been about
1,000 pregnant women in government-sponsored trials to study perinatal
transmission and 13 more are planned or just completed which will
include about 5,000 more pregnant women, studies of anti-HIV or
opportunistic infection treatments exclude pregnant women.

We don't know dosing or dose intervals
for women, though some data exist for pregnant women. Drug labels
do not state whether a drug has been tested in women; they give
this information about pregnant women, children and the "elderly."
We know how pregnancy influences disease progression, but not
how anti-HIV treatments affect infections women get, like cervical
cancer or bacterial pneumonia or how they affect women's renal
functioning, liver functioning, or viral load. Measures of drug
effectiveness are based on men. We don't know how viral load relates
to disease progression in women; we do have some data relating
viral load to perinatal transmission. We don't know how treatments
for infections like lymphoma or MAC affect women. We know that
using fluconazole prevents vaginal yeast infections in women with
HIV but not whether eating yogurt will do the same thing. We don't
know about viral concentrations in women's lymph nodes or about
long term non-progressing women.

We do know that in 1996, AIDS deaths
for women rose while for men they decreased and that survival
times are shorter for women than for men.

The first cases of women with HIV/AIDS
were reported in 1981. After 16 years, I asked myself, why do
we know so little? This question led me to consider my first thought.

I believe there is a national research
policy, but much of it is unspoken. It reflects ideas about women
in general, and about women living with HIV/AIDS in particular,
which seem so natural that, even when spoken, they are accepted
as true without thinking. Changing them is not going to be easy.
But if we want an ethical national research policy which might
extend or save women's lives, we are going to have to create it
based a whole different set of ideas.

I call the ideas which now exist "the
faulty foundations" of current research policies (See Chart 1
left column). As I talk about them, you can contrast them to those
on the right -- what I call the "building blocks"
for an ethical research policy, that is, what a different
set of basic ideas would be. After I go over these, I will propose
some first steps towards a new policy.

Numbers 1-5 are explanations given for
why women were and are not included in clinical or basic research,
why so little women-focused research exists, and why we know so
little. Numbers 1-3 were spoken until about 1990. We have disproved
them, but they still influence, in unspoken ways, what is being
done now.

The MAC study, following 6,000 infected
men, but no women, was federally funded and began in 1983. Almost
everything we know about disease progression and immune system
functioning is based on it. But researchers were denied federal
funding to study women. The government, the medical research establishment,
and drug companies acted like (#1) WOMEN WITH HIV/AIDS DID NOT
EXIST. Around 1987 these institutions had to admit that women
with HIV/AIDS existed, but said (#2) THERE WERE TOO FEW TO BE
INCLUDED IN RESEARCH. But women are almost totally absent from
the phase of pharmacokinetics -- how drugs are absorbed and cleared
by the body -- which influences toxicity, dosing, safety and effectiveness.
Another reason suddenly appeared: (#3) MOST WOMEN ARE IN THE EARLY
STAGES OF DISEASE. However, we don't know if the women were really
asymptomatic. They simply did not have male-defined symptoms.
And, the data were not analyzed by gender anyway.

So, women AIDS activists did the research
and produced the first Women's Treatment and Research Agenda in
1990, in which we discussed TB, vaginal candidiasis, cervical
cancer, MAC, bacterial pneumonia, and more. We pressured the government
to form a Women's Health Committee at the ACTGs, which happened
in 1990, and to do a natural history study of women, comparable
to the MAC study. The WIHS (Women's Interagency HIV Study) was
finally funded in 1991; it began in 1993. We also pressured the
Centers for Disease Control to add women's infections to the definition
of AIDS and as HIV symptoms because numbers of cases based on
those definitions were used to decide what should be studied and
because almost all clinical research required a CDC definition
of AIDS or an HIV symptom as an entry criterion. The CDC capitulated
in 1993, also adding <200 CD4s as an AIDS definer, In the half-year
following, over 9,000 cases in women were reported, an increase
of 34% over cumulative total. In 1996, of 13,820 cases in women,
64.5% fit only the 1993 definition.

However, although we have proven that
lots of women with HIV/AIDS are in various stages of illness,
we still have not seen large numbers of women in clinical or basic
research; we have not seen gender analyses, women-specific studies,
or women-specific measures of drug effectiveness. No government-funded
research team is required to have a women's health specialist.
On the Women's Health Committee, obstetricians and pediatricians
dominate. The ACTG Oncology Committee does not do studies of the
cancers women get. At conferences, as we have seen at this one,
information is presented about treatment outcomes or relating
immune function to progression based on studies with men, although
this is hardly ever stated. When we ask "Is this data based
on women?", the presenters panic. Why can't they even give
us this information? Clearly, ideas 1-3 still influence the research
agenda.

When we raise these issues, we are told
(#4) WOMEN DON'T WANT TO PARTICIPATE IN RESEARCH. Women are suspicious
about medical research -- based on experience and information.
The Tuskeegee syphilis studies are often cited as a reason African-American
women don't want to participate. But we rarely hear about the
experiences poor women, especially Puerto Rican and other Latina
women, have had with doctors coercing them into sterilizations
in exchange for abortions or about how FDA approved research also
produced DES and the Dalkon Shield.

But, still, most of women's lack of participation
is not of their own choosing. There are lots of ways women are
excluded from drug research, for example, trials exclude former
or present drug users. But even if women enter research they are
likely to drop out because they are treated as "subjects"
not as participants -- not given either information about data
being collected from them nor receiving state-of-the-art primary
care -- when these may be why they agreed to participate since
this may be their only way to obtain either.

Miraculously, there have been women who
met study criteria and were desperate to enter a trial to access
experimental therapy, only to be told they would have to be surgically
sterilized in order to participate. This points to a major reason
for women's exclusion from drug research -- the Food and Drug
Administration guidelines and regulations for clinical research.
These are based on several other ideas about women, ideas shared
by researchers and used by drug companies to continue business-as-usual.
One idea is (#5) WOMEN LIVING WITH HIV/AIDS ARE NOT CAPABLE OF
MAKING DECISION ABOUT THEIR OWN LIVES AND ARE IN NEED OF PROTECTION.

The 1977 FDA guidelines excluded women
of "child-bearing potential" from Phase I studies and
from later studies as well unless animal fetal toxicity and reproductive
studies were completed. A woman of "child-bearing potential"
was defined as a menstruating woman capable of becoming pregnant
(even if she used birth control) -- the major age group of women
with HIV/AIDS Entry criteria for AIDS research trials still can
and do exclude "women of child-bearing potential."

Researchers, drug companies, and the
FDA claimed they were and are protecting women and "potential"
fetuses. But they were and are willing to put women and "real"
fetuses at risk in perinatal transmission studies, while excluding
pregnant women from studies of treatments for themselves. And,
more women are at risk, taking drugs tested on men and not labeled
as such. Lack of concern for the fetus and the sexist bias are
clear because men of child-bearing potential are not excluded
or required to be sterilized even when there are known effects
on fetuses if a man's sperm have been exposed to toxic substances.

After more demonstrations by women AIDS
activists, and the filing of a Citizen's Petition charging the
FDA with sex-discrimination, in 1993 the FDA issued a detailed
set of new guidelines about how and why to do gender analyses
in clinical trials. Admitting that the 1977 guidelines were paternalistic,
unnecessary, and put women's lives at risk, all these did was
"lift and the strict limitation" on "women of child-bearing
potential" and "encourage" drug companies to include
them. But they did not require the inclusion of women in research
nor did they require the presentation of data about women for
the approval of a new drug. The FDA admitted these guidelines
would not increase the number of women in trials. And, these guidelines
contained other ideas about women which signaled a continuation
of business-as-usual, #6, 7, and 8.

The first (#6) is that WOMEN ARE ONLY
A SUB-GROUP OF THE POPULATION. In practice this statistical term
means that sometimes the subgroup is put into trials but only
in small numbers unless you have reason to believe you will find
differences. Small numbers mean no meaningful or statistical analyses
of data. So, you never find differences; then you have no reason
to believe you will and the circle continues. For example, Viracept
from Aguron was approved about one month ago, under these guidelines,
based on a study of 33 women and 1,000 men. They claimed there
were no differences.

After more protests, critiques, letter
writing campaigns, and in 1994 a protest at the FDA and the National
Drug Development Task Force Meetings, in September 1995 the FDA
put out, for public comment, proposed amendments to the Investigational
New Drug (IND) and New Drug Approval (NDA) regulations. These
have still not been issued -- one and one-half years later. But,
even if they were, they will hardly change the situation.

They use the word "require"
and they are "regulations" instead of guidelines, but
they all they "require" is_ 1) a drug sponsor who gets
approval to investigate a new drug has to provide a yearly report,
giving the number of people entered in the research by age, race
and gender. But dosing studies last far less than one year, so
all we will get is more proof that women are excluded, after the
fact; and_ 2) for NDAs, which for life-threatening illnesses like
AIDS can be submitted during the second of three phases of testing,
sponsors must provide "evidence" to support the dosing
recommendations on labels, as well as "effectiveness data"
by gender, age and racial subgroups. But this regulation also
specifically states that it does not require the inclusion of
particular numbers of individuals from (you guessed it) "subgroups".
Simply by having a few women or people of color in a study and
stating either that there do not seem to be differences or they
could not be sure, a new drug could still be approved. This may
change labeling so it might say the drug has not been tested adequately
on women. But there is no requirement to label drugs previously
approved.

As long as women are considered only
a subgroup of the population, the lack of information will continue.
Comparative trials require enough numbers of each group to enable
analyses. To scare us, we are told that putting enough women in
research will delay drug approval. This is not a problem about
women. If having enough people to do comparisons will delay things
(and I don't believe it will), and since the last 150 years of
research have been based on male bodies, perhaps we need women-only
studies for the next 150 years and men can take the drugs tested
in our bodies. The response of the researchers and male AIDS activists
to this suggestion is horror, and I myself, believe this would
be unethical. But so is the opposite.

Women as a subgroup reflects two other
faulty ideas (#7 & 8): that THERE ARE NO DIFFERENCES BETWEEN
MEN AND WOMEN and, if there are, THEY ARE ONLY IN AREAS OF REPRODUCTIVE
ORGANS AND FUNCTIONING. Women do get cervical cancer, men don't,
but they are also more likely to get bacterial pneumonia and to
have renal problems. Estrogen affects drug absorption and clearance.
Trials with post-menopausal women or pregnant women eliminate
exactly the thing that makes a difference. Some small studies
point to the outcomes for infected women. Here are two: 10 a recent
Dutch study (Burger, D.M. et al. Pharmacokinetic variability of
zidovudine in HIV-infected individuals: subgroup analysis and
drug interactions. J. of AIDS, 1994, 8(12), 1683-1689) found that
AZT cleared women's bodies 42% slower than men's and this wasn't
due to body weight. Another study, to be a late-breaker at this
conference, found that women taking the same dose of delavirdine
as men were getting more absorbed into their bodies. What does
this mean for toxicity, for combination therapies, for compliance,
for effectiveness? We don't know.

The studies with women enrolled which
do exist are based on idea #9: WOMEN ARE MORE LIKELY TO TRANSMIT
HIV TO OTHERS (BABIES AND MEN, BUT NOT OTHER WOMEN) THAN TO HAVE
HIV TRANSMITTED TO THEM -- even though the opposite is true. Search
the medical indexes under "women and AIDS." In 1989
most papers were about pregnancy and prostitution. This remains
true today. We have studies of viral load in cervicovaginal fluid
but not in a women's lymph nodes. No one really takes woman-to-woman
transmission seriously. Yet, we have one perinatal transmission
study after another, even though the numbers of children with
AIDS was very low before the use of AZT during pregnancy -- about
1/10 the number of women with AIDS. And, if you dare to say this
you risk being called a baby-hater.

But, the absence of research on treatments
addressing women's own health, and the exclusion of pregnant women
from research for treatment for themselves, indicates that the
focus on perinatal transmission trials, as well as the way in
which the research is done, reflects idea #10: ALL WOMEN WITH
HIV/AIDS WANT TO BECOME PREGNANT OR ARE PREGNANT AND SHOULD BE
WILLING TO GIVE UP THEIR HEALTH IN ORDER TO HAVE AN UN INFECTED
CHILD. The ideas of the innocent child and the guilty women are
alive and well in the AIDS research establishment. Pregnant women
who do not want to take AZT or other drugs are considered criminal
by some and ignorant by others. And, their health comes last in
these studies. Recently, women AIDS activists pointed out that
AZT monotherapy is no longer the standard of care for any infected
person and that the perinatal guidelines could be considered bad
medical practice. There are now new draft guidelines but they
also give women unacceptable choices based on no information,
suggesting that due to lack of data from animal fetal toxicity
and reproductive studies, and because of possible genetic damage
to the fetus, women "might" consider stopping combo
therapy for the first 14 weeks of pregnancy. The whole world is
telling PWAs not to miss a dose and pregnant women are being given
this advice. Why didn't the FDA require these studies before approving
the drugs?

These guidelines are not about reproductive
choices. Neither are perinatal trials planned in Thailand, the
Ivory Coast and Uganda, for several thousand pregnant women, all
of which compare AZT monotherapy to placebo. Even if we don't
deal with the AZT monotherapy part of these studies, how could
the NIH and the CDC knowingly fund research which allows women
to transmit HIV to their children when they could prevent 2/3
of these cases according to their own research? And, given the
high cost of these drugs, who is the research really for? Are
WOMEN LIVING WITH HIV/AIDS IN OTHER COUNTRIES EXPENDABLE? (#11).

This question leads to #12. When asked
why these perinatal trials were using placebos and not comparing
AZT to combos, one response was that they need to have a group
of high transmitters to show the differences statistically. When
researchers do not see women living with HIV/AIDS as human beings,
but merely "research subjects", SCIENCE BECOMES MORE
IMPORTANT THAN LIFE. But good science does not have to sacrifice
lives.

Even if federal agencies, researchers
and others agree that what we know about women is little and yes,
"they hear our anger", and yes, there is room for improvement,
they tell us (#13) there is no money and (#14) it will take time.
There is money for perinatal trials, for the WITS (Women and Infants
Transmission Study), for the MAC. There is separate pediatric
ACTG -- though I do not think their research is any better. The
quality of research is an issue. One researcher at an ACTG meeting,
seeing my frustration, said: "You want cutting edge research,
but what we do here is mediocre research." We are told that
our complaints about the WIHS study, as it is designed to run,
is also mediocre research. It is quickly becoming another transmission
study -- never one of its goals. It has no state of the art immunology
or virology.

If you believe that the lives of all
people living with HIV/AIDS are equally valuable, put expertise
and money into women's lives too because women living with HIV/AIDS
don't have any more time to wait than anyone else. Women can't
wait another ten years for useless or anachronistic information
or for people to care about keeping them alive or about why they
died.

We must completely refocus our research
policy, programs, and funding. Each of you had, on your seat when
you came in, a paper with an initial set of recommendations for
an ethical national research policy for women living with HIV/AIDS
(See second chart). I will summarize them and you can read them
when you have the time.

Right now, with no acts of Congress,
no changes in regulations, in fact with only a telephone call
or e-mail, everything on the first page could be implemented and
move us incredibly far ahead. Donna Shalala and Sandy Thurmond
should put their political will and control of money where their
mouths are -- give priority to funding AIDS research for women
and get all Public Health Service Agency heads who control any
research money to have a plan for implementing this priority within
the next month. They are asked to do this sort of thing all the
time. The NIH has the power, right now, to require that all of
their funded research include enough women to do gender analysis,
use women-specific measures in all studies and study women's infections,
as well as to mandate women's health specialists on all research
teams. If we can't wait for the FDA to force the drug companies
to do fetal toxicity and reproductive studies for drugs already
approved, the NIH can contract them out and we can have the information
within a few months. If the WIHS study cannot quickly produce
state-of-the-art immunological and virological data and relate
it to disease progression and treatment, give that part of the
study to the MAC, add a women's health specialist to their teams,
and pay them to do it. And, put knowledgeable women living with
HIV/AIDS on all grant review panels.

The second set of recommendations are
for the FDA: Above all they should create regulations requiring
the inclusion of enough women in clinical trials to allow meaningful
analyses and requiring meaningful gender analyses for drug approval.
They must find a way to force drug sponsors to do animal studies
before they can test the drug in humans and let women and men
decide what they want to do based on the information. All drugs
previously approved must be immediately labeled stating they were
not tested in women. And, women living with HIV/AIDS, who are
knowledgeable, must be placed on all FDA, IND and NDA approval
panels.

It is past due time for research about
and for women living with HIV/AIDS, research of the highest quality,
which speaks to women's bodies and needs and designed around women's
lives. Women living with HIV/AIDS need research which allows real
reproductive choice but they must not be viewed as only reproductive
machines or transmitters to babies and men.

If the answer to the question -- "Who
is "The Cure" for?" is truly to be "It's for
everyone", we must not simply ask for, but must demand
research to save women's lives.